Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/117658
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dc.contributor.authorJiang, H.en
dc.contributor.authorNewman, M.en
dc.contributor.authorLardelli, M.en
dc.date.issued2018en
dc.identifier.citationPLoS ONE, 2018; 13(10):e0206155-1-e0206155-20en
dc.identifier.issn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/2440/117658-
dc.description.abstractAlzheimer's disease is the most common form of age-related dementia. At least 15 mutations in the human gene PRESENILIN 2 (PSEN2) have been found to cause familial Alzheimer's disease (fAD). Zebrafish possess an orthologous gene, psen2, and present opportunities for investigation of PRESENILIN function related to Alzheimer's disease. The most prevalent and best characterized fAD mutation in PSEN2 is N141I. The equivalent codon in zebrafish psen2 is N140. We used genome editing technology in zebrafish to target generation of mutations to the N140 codon. We isolated two mutations: psen2N140fs, (hereafter "N140fs"), causing truncation of the coding sequence, and psen2T141_L142delinsMISLISV, (hereafter "T141_L142delinsMISLISV"), that deletes the two codons immediately downstream of N140 and replaces them with seven codons coding for amino acid residues MISLISV. Thus, like almost every fAD mutation in the PRESENILIN genes, this latter mutation does not truncate the gene's open reading frame. Both mutations are homozygous viable although N140fs transcripts are subject to nonsense-mediated decay and lack any possibility of coding for an active γ-secretase enzyme. N140fs homozygous larvae initially show grossly normal melanotic skin pigmentation but subsequently lose this as they grow while retaining pigmentation in the retinal pigmented epithelium. T141_L142delinsMISLISV homozygotes retain faint skin melanotic pigmentation as adults, most likely indicating that the protein encoded by this allele retains weak γ-secretase activity. Null mutations in the human PRESENILIN genes do not cause Alzheimer's disease so these two mutations may be useful for future investigation of the differential effects of null and fAD-like PRESENILIN mutations on brain aging.en
dc.description.statementofresponsibilityHaowei Jiang, Morgan Newman, Michael Lardellien
dc.language.isoenen
dc.publisherPublic Library Scienceen
dc.rights© 2018 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectZebrafish; embryos; polymerase chain reaction; fish; insertion mutation; hypoxia; mutation; frameshift mutationen
dc.titleThe zebrafish orthologue of familial Alzheimer's disease gene PRESENILIN 2 is required for normal adult melanotic skin pigmentationen
dc.typeJournal articleen
dc.identifier.rmid0030101964en
dc.identifier.doi10.1371/journal.pone.0206155en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1061006en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1126422en
dc.identifier.pubid445826-
pubs.library.collectionGenetics publicationsen
pubs.library.teamDS10en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidNewman, M. [0000-0002-4930-4529]en
dc.identifier.orcidLardelli, M. [0000-0002-4289-444X]en
Appears in Collections:Genetics publications

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